The aim of this study was to analyze the temporal trend of leptospirosis incidence according to rainfall levels in Santa Catarina State between 2005 and 2015. This is an ecological time-series study involving data on leptospirosis incidence and rainfall indexes in Santa Catarina State Health Regions. The distribution of leptospirosis, rainfall indexes, and cases/rainfall ratios, according to seasonality and stratified by Health Regions, were evaluated. There were 5,274 cases, with an average rate of 7.03 cases/100,000 inhabitants per year, varying from 24 to 1,458 cases (Serra Catarinense and Northeast regions, respectively) in Santa Catarina, revealing an increase in the rates of 0.70 cases/100,000 inhabitants in Serra Catarinense and 13.99 cases/100,000 inhabitants in the Northeast. Four regions (Foz do Rio Itajaí, Médio Vale do Itajaí, Grande Florianópolis and Northeast) were responsible for 71.8% of the cases, particularly in the Northeast region (38.5%). The five regions with the highest rates presented greater risk of leptospirosis (RR > 1), ranging from 10.9 to 19.9 more new cases of the disease. The average rainfall volume for Santa Catarina State was 158.69 mm, ranging from 136.44 mm in Laguna to 186.81 mm in the Northeast. The five regions contributed with 32.8% of the rainfall index accumulated in the period. In conclusion, leptospirosis occurred all around Santa Catarina State, differing its temporal trend according to the Health Regions. The aim of this study was to analyze the temporal trend of leptospirosis incidence according to rainfall levels in Santa Catarina State between 2005 and 2015. This is an ecological time-series study involving data on leptospirosis incidence and rainfall indexes in Santa Catarina State Health Regions. The distribution of leptospirosis, rainfall indexes, and cases/rainfall ratios, according to seasonality and stratified by Health Regions, were evaluated. There were 5,274 cases, with an average rate of 7.03 cases/100,000 inhabitants per year, varying from 24 to 1,458 cases (Serra Catarinense and Northeast regions, respectively) in Santa Catarina, revealing an increase in the rates of 0.70 cases/100,000 inhabitants in Serra Catarinense and 13.99 cases/100,000 inhabitants in the Northeast. Four regions (Foz do Rio Itajaí, Médio Vale do Itajaí, Grande Florianópolis and Northeast) were responsible for 71.8% of the cases, particularly in the Northeast region (38.5%). The five regions with the highest rates presented greater risk of leptospirosis (RR > 1), ranging from 10.9 to 19.9 more new cases of the disease. The average rainfall volume for Santa Catarina State was 158.69 mm, ranging from 136.44 mm in Laguna to 186.81 mm in the Northeast. The five regions contributed with 32.8% of the rainfall index accumulated in the period. In conclusion, leptospirosis occurred all around Santa Catarina State, differing its temporal trend according to the Health Regions.